Evaluation of antimicrobial stewardship activities using antibiotic spectrum coverage

Recently, the days of antibiotic spectrum coverage (DASC) using the antibiotic spectrum coverage (ASC) score was reported as a new tool for measuring antimicrobial use. The days of therapy (DOT) are required to calculate the DASC, making it impossible to use when patient-level information is unavailable. Therefore, we have defined a new measure of antimicrobial use for antimicrobial spectrum coverage (AUSC) using antimicrobial use density (AUD) and ASC scores. In this study, we have investigated the use of antimicrobial agents retrospectively examined for monthly prescriptions between 2016 and 2022, and whether the AUSC could be used as a new measure. Our data showed that the AUD, AUSC, DOT, and DASC increased, whereas AUSC/AUD and DASC/DOT decreased over the study period. In addition, no correlation was found between DOT and DASC/DOT (ρ = − 0.093, p = 0.399), whereas there was a weak correlation between AUD and AUSC/AUD (ρ = − 0.295, p = 0.006). Therefore, in this study, the use of AUSC is considered less beneficial when DASC can be calculated based on DOT. On the other hand, in institutional settings where DOT cannot be calculated, AUSC may be useful as a new measure to evaluate antimicrobial use.


Antimicrobial stewardship
During the observation period, the AS was led by one board-certified infection control pharmacy specialist (0.5 full-time equivalents [FTE]), one to two infectious disease physicians (total, 0.8 FTE), one clinical laboratory technician (0.5 FTE), and one to two nurses (total, 0.3 FTE).The total FTE for AS members was 2.0 FTE.AS monitored all inpatients for antimicrobial use and provided feedback every weekday.The number of interventions for the prescription of antimicrobial agents by the AS had a mean of 736.2 ± 301 (standard deviation) interventions per month.The number of recommendations for antimicrobial selection by AS had a mean of 67.0 ± 30.7 interventions per month; for de-escalation, 21.6 ± 15.6; for dose changes, 10.3 ± 8.4; and for stopping antimicrobial therapy, 11.8 ± 8.5.The acceptance rate of recommendations during the reporting period was 95.5%.

Data collection
The AMR surveillance system is the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) 12 .The AUD and DOT were calculated using the J-SIPHE application from the EF combined file, which consisted of the E file (medical treatment details) and F file (medical action details) used for medical billing in the Diagnosis Procedure Combination practice.The AUD and DOT can be calculated by submitting the EF files and using data files in the J-SIPHE application.
Additionally, the AUSC and DASC were calculated using the ASC scores defined in previous studies 10,13 .Furthermore, we calculated the AUSC/AUD and DASC/DOT, representing the average antibiotic spectrum provided to hospital inpatients.Patients treated with antiviral or antifungal agents for which ASC scores are yet to be determined were excluded.The definitions of the AUD, DOT, DASC, and AUSC are as follows: Antimicrobial use density: (AUD) = [(total usage/defined daily dose) / (total number of patient days)] × 100.Days of therapy: (DOT) = [total days used/total number of patient days] × 100.Antimicrobial use for antimicrobial spectrum coverage: AUSC = antimicrobial use density × antibiotic spectrum coverage score.Days of antibiotic spectrum coverage: DASC = days of therapy × antibiotic spectrum coverage score.

Statistical analysis
We statistically analyzed trends in AUD, AUSC, AUSC/AUD, DOT, DASC, and DASC/DOT using linear regression.The regression coefficient β, 95% confidence interval (CI), and coefficient of determination R 2 were used to calculate whether there was an increase or decrease.In addition, Spearman's correlation analysis was used to calculate the coefficient (ρ) of correlations between AUD, AUSC, and AUSC/AUD and between DOT, DASC, and DASC/DOT.SPSS version 24 (SPSS, Chicago, IL, USA) was used for all of the analyses.

Discussion
AUD and DOT do not reflect the spectrum of antimicrobial agents.In contrast, AUSC and DASC, including the ASC score, are composite metrics that simultaneously measure antimicrobial consumption and spectrum.AUSC is a new definition calculated from the AUD and ASC scores.This study examined its potential as a new definition following AUD, DOT, and DASC.This study suggests that AUSC may be used as an alternative to  DASC as a spectrum indicator of antimicrobials in situations where DOT cannot be calculated.However, it should be noted that AUSC is affected by DDD and may not directly reflect the ASC score compared to DASC.In this study, the total AUD and DOT increased during the study period.Carbapenems, fluoroquinolones, and aminoglycosides decreased AUD and DOT.In contrast, the AUD and DOT of penicillin and first-, third-, and fourth-generation cephalosporins, oxacephems, and cephamycins tended to increase.This suggests a shift towards more narrow-spectrum antimicrobial agents.This was indicated by the fact that AUSC/AUD and DASC/ DOT decreased over this period.
This study evaluated a new definition of AUSC.The AUSC is an indicator that reflects the AUD and antimicrobial spectrum and is relatively easy to calculate, even in situations where the DOT cannot be calculated.During the study period, there was a significant increase in both AUSC and DASC.The potential reduced impact of the ASC score compared to the DASC should be considered when interpreting the AUSC.When considering antimicrobials with the same ASC score, one administered at a dose below the DDD would receive a lower AUSC score compared to another administered at a standard dose.Therefore, incorporating the concept of DDD into spectrum coverage indicators could make it impossible to accurately calculate spectrum coverage.In contrast, DASC is considered a more appropriate spectrum coverage indicator than AUSC because the ASC score is directly reflected in the spectrum coverage index.In Japan, the recommended dosage of some antimicrobial agents is set lower than the DDD.In this study, AUD/DOT was less than 1 (monthly mean 0.75 ± 0.03) and the daily dose was less than DDD.The discrepancy between the recommended dosage and the DDD may be the reason why the benefit of AUSC could not be derived.
Furthermore, significant decreases in AUSC/AUD and DASC/DOT may be due to a decrease in the unnecessary use of broad-spectrum antimicrobial agents in empirical therapy and a shift to narrow-spectrum antimicrobial agents, consistent with the AUD and DOT results.This suggests that AUSC/AUD and DASC/DOT can be used as indicators of de-escalation.When the DOT and DASC cannot be calculated, combining AUD as a usage indicator and AUSC/AUD as a spectrum indicator may be a more appropriate way to evaluate AS efforts.
On the other hand, DASC/DOT did not correlate with DOT.This study also suggests that the DASC/DOT can be employed as an independent indicator for evaluating the spectrum of antimicrobial agents used, as evidenced by previous studies 11 .However, a weak correlation was observed between AUSC/AUD and AUD, suggesting that AUSC/AUD was influenced by variations in DDD.
This study had several limitations.First, this was a single-center study in Tokyo, Japan, and the feasibility of these findings as indicators for evaluating antimicrobial agents in other centers needs to be investigated.Second, this study could not examine differences in patient backgrounds, such as disease type and severity, during the study period.Cefazolin is recommended for treating Staphylococcus aureus (S. aureus) bacteremia for 14 days for uncomplicated infections and 4-8 weeks for complicated infections, including infective endocarditis [14][15][16][17][18] .Combined and long-term antimicrobial therapies are recommended to treat infective endocarditis and other complicated infections.Consequently, AUDs and DOTs are high even with appropriate antimicrobial therapy, and it is unclear how the patients' backgrounds affect the changes in AUD and DOT.Third, the spectrum of antimicrobial agents available for treating antimicrobial-resistant bacteria, such as extended-spectrum β-lactamaseproducing bacteria and methicillin-resistant S. aureus, is broader than that for treating bacterial infections caused by antimicrobial-susceptible strains 19 .However, the present study did not examine the relationship between the number of resistant bacteria and AUSC or DASC.Finally, this study did not consider the COVID-19 pandemic.

Table 1 .
Comparing AUD and DOT trends at NTT Medical Center Tokyo between 2016 and 2022.AUD antimicrobial use density, DOT days of therapy, β regression coefficient, R 2 determination coefficient, CI confidence interval.